The combination of cetuximab and FOLFIRI is active in gastric and GEJ adenocarcinoma. The higher toxicity appears to be limited to neutropenia.

Gastric cancer (GC) represents the fifth most frequently diagnosed cancer worldwide, with a poor prognosis in patients with advanced disease despite many improvements in systemic treatments in the last decade. In fact, GC has shown resistance to several treatment options, and thus, notable efforts have been focused on the research and identification of novel therapeutic targets in this setting. The tumor microenvironment (TME) has emerged as a potential therapeutic target in several malignancies including GC, due to its pivotal role in cancer progression and drug resistance. Therefore, several agents and therapeutic strategies targeting the TME are currently under assessment in both preclinical and clinical studies. The present study provides an overview of available evidence of the inflammatory TME in GC, highlighting different types of tumor-associated cells and implications for future therapeutic strategies.

BACKGROUND: The conventional treatment options for advanced gastric patients remain unsatisfactory in terms of response rate, response duration, toxicity, and overall survival benefit. The purpose of this phase II study was to evaluate the activity and safety of cetuximab combined with cisplatin and docetaxel as a first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma. METHODS: Untreated patients with histologically confirmed advanced gastric or gastro-oesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg m À2 i.v. followed by weekly doses of 250 mg m À2 , cisplatin 75 mg m À2 i.v. on day 1, docetaxel 75 mg m À2 i.v. on day 1, every 3 weeks, for a maximum of 6 cycles, and then cetuximab maintenance treatment was allowed in patients with a complete response, partial response, or stable disease. RESULTS: Seventy-two patients (stomach 81.9% and gastro-oesophageal junction 18.1%; locally advanced disease 4.2%; and metastatic disease 95.8%) were enrolled. The ORR was 41.2% (95% CI, 29.5 -52.9). Median time to progression was 5 months (95% CI, 3.7 -5.4). Median survival time was 9 months (95% CI, 7 -11). The most frequent grades 3 -4 toxicity was neutropenia (44.4%). No toxic death was observed. CONCLUSIONS: The addition of cetuximab to the cisplatin/docetaxel regimen improved the ORR of the cisplatin/docetaxel doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS. The toxicity of cisplatin/docetaxel chemotherapy was not affected by the addition of cetuximab.

Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in approximately 15–20% of gastric adenocarcinoma (GC) patients. In 2010, the landmark ToGA trial established the combination of trastuzumab plus chemotherapy as the first-line standard of care for HER2-positive GC patients with advanced disease. However, subsequent studies on HER2 targeted therapies in this setting failed to meet their primary endpoints, and not all HER2-positive GC patients benefit from targeted approaches. More recently, novel HER2-directed treatments have been investigated, including trastuzumab deruxtecan (T-Dxd); following the results of the DESTINY-Gastric01 study, T-Dxd received its first U.S. Food and Drug Administration (FDA) approval on 15 January 2021 for the treatment of adults with unresectable, locally advanced, or metastatic GC who have received a prior trastuzumab-based regimen. In this review, we discuss the current HER2-targeted treatments for GC in the advanced disease setting, mainly focusing on emerging new treatments and future research directions.

Background:The aim of the PROMETEO-01 Study was to define the diagnostic accuracy of imaging techniques in colorectal cancer liver metastasis (CRCLM) patients.Methods:Patients referred to Bologna S. Orsola-Malpighi Hospital performed a computed-tomography scan (CT), magnetic resonance (MR), 18F-FDG-PET/CTscan (PET/CT) and liver contrast-enhanced-ultrasound (CEUS); CEUS was also performed intraoperatively (i-CEUS). Every pathological lesion was compared with imaging data.Results:From December 2007 to August 2010, 84 patients were enrolled. A total of 51 (60.71%) resected patients were eligible for analysis. In the lesion-by-lesion analysis 175 resected lesions were evaluated: 67(38.3%) belonged to upfront resected patients (group-A) and 108 (61.7%) to chemotherapy-pretreated patients (group-B). In all patients the sensitivity of MR proved better than CT (91% vs 82% P=0.002), CEUS (91 vs 81% P=0.008) and PET/CT (91% vs 60% P=0.000), whereas PET/CT showed the lowest sensitivity. In group-A the sensitivity of i-CEUS, MR, CT, CEUS and PET/CT was 98%, 94%, 91%, 84% and 78%, respectively. In group-B the i-CEUS proved equivalent in sensitivity to MR (95% and 90%, respectively, P=0.227) and both were significantly more sensitive than other procedures. The CT sensitivity in group-B was lower than in group-A (77% vs 91%, P=0.024).Conclusions:A thoraco-abdominal CT provides an adequate baseline evaluation and guides judgment as to the resectability of CRCLM patients. In the subset of candidates for induction chemotherapy to increase the chance of liver resection, the most rational approach is to add MR for the staging and restaging of CRCLM.